Personalized medicine—and personalized vaccines, in particular—have generated tremendous interest. Each vaccine must be custom-made for each patient, so for each patient more work must be done than is required for "off-the-shelf" vaccines. What are needed now are methods that enable the manufacture of such products in an affordable and efficient manner.

Immunotherapies fall into two categories: passive and active. Active immunotherapies, such as Biovest's BiovaxID, an active immunotherapy currently being tested in a pivotal Phase III trial for the treatment of indolent follicular non-Hodgkin's lymphoma, train the immune system to recognize and remember target cells. In this manner, they destroy the diseased cells while sparing the healthy cells and remain poised to fight off recurrences. Once activated by BiovaxID, for example, a patient's immune system gains a long-lasting memory of the cancer cells and can destroy them if they recur.

Passive immunotherapies, in contrast, rely on administering short-lived immune activators (immunoglobulins or immunoglobulin-like proteins) that help the patient's immune system recognize and destroy specific target cells, including some types of cancer cells. Most passive immunotherapies are "off-the-shelf" products that focus the immune system on molecules believed to be either unique to or abundant on specific types of cancer cells.

For example, Rituxan, which is used to treat B-cell lymphomas, is an immune activator that causes the immune system to destroy cells that have CD20 on their surface. While CD20 is present on the surface of the cancerous lymphocytes, it is also present on normal lymphocytes. Thus, the administration of Rituxan results in the destruction of all B lymphocytes, which can cause serious side effects.

Additionally, once the administration of the immune activators is stopped, the patient has no protection against residual cancer cells that may have survived the therapy. Unless the passive immunotherapy is successful in eliminating 100 percent of the cancer cells, the cancer could recur, requiring successive treatments.

The challenge for active immunotherapies has been in the identification of cellular markers unique to the target cancer cells. It is safe to say there are only one or two types of cancer for which this criterion can be met, the most prominent being non-Hodgkin's B-cell lymphoma. In such a case, the cancerous cells carry up to 150,000 copies of an immunoglobulin molecule unique to the cancer cells; the specific immunoglobulin or idiotype is absent from all other cells in the body, including other B lymphocytes.

Because the marker is unique to each patient's cancer cells, the immune therapy must be tailored to each patient. BiovaxID, for example, starts with a small sample or biopsy of each patient's lymphoma cells to produce characteristic marker immunoglobulin proteins using hybridoma technology. These patient- and cancer-specific marker proteins form the foundation of the vaccine.

Only when these vaccine development methods are coupled with sophisticated new instrumentation and innovative manufacturing paradigms can the promise of personalized medicine become a reality. By developing and using such instruments, Biovest hopes to usher in a new era in medicine, one in which diseased cells are destroyed but normal cells are spared, and in which custom therapies are as affordable as off-the-shelf varieties.

Dr. Carl M. Cohen is COO of Biovest International, having joined the company in December 2004. A graduate of Harvard University, he previously held positions as vice president of research at Acumen Sciences LLC and vice president for research and development at Creative BioMolecules.